Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

HIV-infected pregnant women were recruited from antenatal clinics at DAIDS Clinical Trials Sites in Zimbabwe, South Africa, Uganda & Tanzania between May 14, 2008 & January 20th 2010. 1700 mother/infant pairs were enrolled & infants were given daily doses of Nevirapine for 6 weeks at which point there were randomized to placebo or extended NVP.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

Infants were excluded from randomization if in first 42 days: had a positive HIV-1 DNA PCR, breastfeeding was discontinued, never initiated or permanently discontinued open-label NVP, certain graded abnormal labs, skin rash grade2B or higher, clinical hepatitis, serious illness/condition that prevented compliance, or use of rifampin/ketoconazole.

Reporting Groups

Description

Placebo

For infants: extended treatment with NVP placebo

Nevirapine

For infants: extended treatment with NVP

Participant Flow: Overall Study

Placebo

Nevirapine

STARTED

763
[1]

759
[1]

Week 8 Visit

759

759

Month 3 Visit

759

755

Month 4 Visit

758

752

Month 5 Visit

756

750

Month 6 Visit

748

748

Month 9 Visit

741

741

Month 12 Visit

733

735

COMPLETED

681
[2]

675
[2]

NOT COMPLETED

82

84

Death

30

26

Lost to Follow-up

52

58

[1]

Number of infants randomized at 6 weeks.

[2]

Number of infants who completed final 18 month visit: out of 733 infants who were expected.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

A total of 1527 infants were randomized to either placebo or extended NVP. 5 of these infants were later found to be infected at the time of randomization (2 in NVP and 3 in Placebo). Thus, only 1522 infants were included in the analysis.

Reporting Groups

Description

Nevirapine

For infants: extended treatment with NVP

Placebo

For infants: extended treatment with NVP placebo

Measured Values

Nevirapine

Placebo

Number of Participants Analyzed
[units: participants]

759

763

Relative Rates of HIV Infection in the Two Arms
[units: participants]

# of infants with HIV infection at 18 months

16

23

# of infants @ risk for HIV infection at 18 months

664

663

Statistical Analysis 1 for Relative Rates of HIV Infection in the Two Arms

Groups [1]

Nevirapine

Method [2]

Kaplan-Meier Method

18 mon. Rate of Cum HIV Infection (%) [3]

2.2

95% Confidence Interval

( 1.1 to 3.3 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The cumulative rate of HIV infection at 18 months in the extended NVP arm was calculated using the Kaplan-Meier method; while the 95% confidence interval was calculated using Greenwood's formula.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

No text entered.

[3]

Other relevant estimation information:

No text entered.

Statistical Analysis 2 for Relative Rates of HIV Infection in the Two Arms

Groups [1]

Placebo

Method [2]

Kaplan-Meier Method

18 mon. Rate of Cum. HIV Infection (%) [3]

3.1

95% Confidence Interval

( 1.9 to 4.4 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The cumulative rate of HIV infection at 18 months in the placebo arm was calculated using the Kaplan-Meier method; while the 95% confidence interval was calculated using Greenwood's formula.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

No text entered.

[3]

Other relevant estimation information:

No text entered.

Statistical Analysis 3 for Relative Rates of HIV Infection in the Two Arms

Groups [1]

All groups

Method [2]

Z-test

P Value [3]

0.280

Z statistic [4]

1.081

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The cumulative rates of HIV infection at 18 months were calculated using the Kaplan-Meier method and were compared between arms using a Z statistic.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

No text entered.

[3]

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

P-value was not adjusted for interim analysis or multiple testing.

[4]

Other relevant estimation information:

No text entered.

5. Secondary:

Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms [ Time Frame: At Month 18 ]

Limitations of the study, such as early termination leading to small numbers of participants
analyzed and technical problems with measurement leading to unreliable or uninterpretable data

The rate of maternal highly active antiretroviral therapy use was higher than expected in our study. Thus there were fewer infant infections which decreased the power to detect differences in HIV transmission risks between study groups.